Aberrant Motility in Unaffected Small Bowel is Linked to Inflammatory Burden and Patient Symptoms in Crohn's Disease.

BACKGROUND: Inflammation-related enteric dysmotility has been postulated as a cause for abdominal symptoms in Crohn's disease (CD). We investigated the relationship between magnetic resonance imaging-quantified small bowel (SB) motility, inflammatory activity, and patient symptom burden. METHODS: The Harvey-Bradshaw index (HBI) and fecal calprotectin were prospectively measured in 53 patients with CD (median age, 35; range, 18-78 years) the day before magnetic resonance enterography, which included a dynamic (cine), breath-hold motility sequence, repeated to encompass the whole SB volume. A validated registration-based motility quantitation technique produced motility maps, and regions of interest were drawn to include all morphologically normal SB (i.e., excluding diseased bowel). Global SB motility was correlated with calprotectin, HBI, and symptom components (well-being, pain, and diarrhea). Adjustment for age, sex, smoking, and surgical history was made using multivariate linear regression. RESULTS: Median calprotectin was 336 (range, 0-1280). Median HBI, motility mean, and motility variance were 3 (range, 0-16), 0.33 (0.18-0.51), and 0.01 (0.0014-0.034), respectively. Motility variance was significantly negatively correlated with calprotectin (rho = -0.33, P = 0.015), total HBI (rho = -0.45, P 0.05). CONCLUSIONS: Reduced motility variance in morphologically normal SB is associated with patient symptoms and fecal calprotectin levels, supporting the hypothesis that inflammation-related enteric dysmotility may explain refractory abdominal symptoms in CD

Assessment of body composition and association with clinical outcomes in patients with lung and colorectal cancer

OBJECTIVES: To assess body composition in patients with non-small cell lung cancer (NSCLC) and colorectal cancer using whole-body MRI and relate this to clinical outcomes. METHODS: 53 patients with NSCLC (28 males, 25 females; mean age 66.9) and 74 patients with colorectal cancer (42 males, 32 females; mean age 62.9) underwent staging whole-body MRI scans, which were post-processed to derive fat mass (FM), fat free mass (FFM) and skeletal muscle (SM) indices and SM fat fraction (FF). These were compared between the two cancer cohorts using two-sided t-tests and the chi-squared test. Measurements of body composition were correlated with outcomes including length of hospital stay, metastatic status and mortality. RESULTS: Patients with NSCLC had significantly lower FFM (p = 0.0071) and SM (p = 0.0084) indices. Mean SM FF was greater in patients with NSCLC (p = 0.0124) and was associated with longer hospital stay (p = 0.035). There was no significant relationship between FM, FFM and SM indices and length of hospital stay, metastatic status or mortality. CONCLUSIONS: Patients with NSCLC had lower FFM and SM indices than patients with colorectal cancer and greater SMFF, indicating lower SM mass with fatty infiltration. These findings reflect differences in the phenotype of the two groups and suggest patients with lung cancer are more likely to require additional nutritional support. ADVANCES IN KNOWLEDGE: Body composition differs between NSCLC and colorectal cancer. Patients with NSCLC have both a reduced SM mass and greater SM FF suggesting that they are more nutritionally deplete than patients with colorectal cancer

Hand-portable HPLC with broadband spectral detection enables analysis of complex polycyclic aromatic hydrocarbon mixtures

Polycyclic aromatic hydrocarbons (PAHs) are considered priority hazardous substances due to their carcinogenic activity and risk to public health. Strict regulations are in place limiting their release into the environment, but enforcement is hampered by a lack of adequate field-testing procedure, instead relying on sending samples to centralised analytical facilities. Reliably monitoring levels of PAHs in the field is a challenge, owing to the lack of field-deployable analytical methods able to separate, identify, and quantify the complex mixtures in which PAHs are typically observed. Here, we report the development of a hand-portable system based on high-performance liquid chromatography incorporating a spectrally wide absorption detector, capable of fingerprinting PAHs based on their characteristic spectral absorption profiles: identifying 100% of the 24 PAHs tested, including full coverage of the United States Environmental Protection Agency priority pollutant list. We report unsupervised methods to exploit these new capabilities for feature detection and identification, robust enough to detect and classify co-eluting and hidden peaks. Identification is fully independent of their characteristic retention times, mitigating matrix effects which can preclude reliable determination of these analytes in challenging samples. We anticipate the platform to enable more sophisticated analytical measurements, supporting real-time decision making in the field

Patient deprivation and perceived scan burden negatively impact on the quality of WB-MRI

Aim: To evaluate the association between cancer staging whole body WB-MRI (WB-MRI) image quality and patient demographics, distress and perceived scan burden Materials and Methods: A sample of patients prospectively recruited to multicentre trials comparing WB-MRI with standard scans for staging lung and colorectal cancer, were invited to complete two questionnaires. The baseline questionnaire, administered at recruitment, collated data on demographics, distress and co-morbidity; the follow-up questionnaire, completed after staging investigations, measured perceived WB-MRI scan burden (scored 1 low to 7 high). WB-MRI anatomical coverage and technical quality was graded by a radiographic technician and grading combined to categorise the scan as ‘optimal’, ‘sub-optimal’ or ‘degraded’. A radiologist categorised 30 scans to test inter-observer agreement. Data were analysed using Chi Square, Fisher Exact, t-tests and multinomial regression. Results: 114 patients were included in the study (53 lung, 61 colorectal; average age 65.3, SD=11.8; 66 men, (57.9%)). Overall, 45.6% (n=52), scans were classified as ‘optimal’ quality, 39.5% (n=45) ‘sub-optimal’ and 14.9% (n=17) as ‘degraded’. In adjusted analyses greater deprivation level and higher patient-reported scan burden were both associated with a higher likelihood of having a sub-optimal vs. an optimal scan (OR: 4.465, CI: 1.454 to 13.709, p=0.009; OR: 1.987, CI: 1.153 to 3.425, p=0.013 respectively). None of the variables predicted the likelihood of having a degraded scan. Conclusions: Deprivation as well as patients’ perceived experience of the WB-MRI, is related to image quality. Tailored protocols and individualised patient management before and during WB-MRI may improve scan quality

Estimation of contrast agent bolus arrival delays for improved reproducibility of liver DCE MRI

Delays between contrast agent (CA) arrival at the site of vascular input function (VIF) sampling and the tissue of interest affect dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling. We investigate effects of altering VIF CA bolus arrival delays on liver DCE MRI perfusion parameters, propose an alternative approach to estimating delays and evaluate reproducibility. Thirteen healthy volunteers (28.7  ±  1.9 years, seven males) underwent liver DCE MRI using dual-input single compartment modelling, with reproducibility (n  =  9) measured at 7 days. Effects of VIF CA bolus arrival delays were assessed for arterial and portal venous input functions. Delays were pre-estimated using linear regression, with restricted free modelling around the pre-estimated delay. Perfusion parameters and 7 days reproducibility were compared using this method, freely modelled delays and no delays using one-way ANOVA. Reproducibility was assessed using Bland–Altman analysis of agreement. Maximum percent change relative to parameters obtained using zero delays, were  −31% for portal venous (PV) perfusion, +43% for total liver blood flow (TLBF), +3247% for hepatic arterial (HA) fraction, +150% for mean transit time and  −10% for distribution volume. Differences were demonstrated between the 3 methods for PV perfusion (p  =  0.0085) and HA fraction (p  <  0.0001), but not other parameters. Improved mean differences and Bland–Altman 95% Limits-of-Agreement for reproducibility of PV perfusion (9.3 ml/min/100 g, ±506.1 ml/min/100 g) and TLBF (43.8 ml/min/100 g, ±586.7 ml/min/100 g) were demonstrated using pre-estimated delays with constrained free modelling. CA bolus arrival delays cause profound differences in liver DCE MRI quantification. Pre-estimation of delays with constrained free modelling improved 7 days reproducibility of perfusion parameters in volunteers

MRI texture analysis parameters of contrast-enhanced T1-weighted images of Crohn's disease differ according to the presence or absence of histological markers of hypoxia and angiogenesis

PURPOSE: To investigate if texture analysis parameters of contrast-enhanced MRI differ according to the presence of histological markers of hypoxia and angiogenesis in Crohn's disease (CD). METHODS: Seven CD patients (mean age 38 (19-75), 3 male)) undergoing ileal resection underwent 3T MR enterography including axial ultrafast spoiled gradient-echo T1 post IV gadolinium chelate. Regions of interest were placed in bowel destined for resection and registered to trans-mural histological sections (n = 28 across 7 bowel sections) via MRI of the resected specimen. Microvessel density (MVD) and staining for markers of hypoxia (HIF 1α) and angiogenesis (VEGF) were performed. Texture analysis features were derived utilizing an image filtration-histogram technique at spatial scaling factor (SSF) 0-6 mm, including mean, standard deviation, mean of positive pixels, entropy, kurtosis and skewness and compared according to the presence or absence of histological markers of hypoxia/angiogenesis using Mann-Whitney U/Kruskal-Wallis tests and with the log of MVD using simple linear regression. RESULTS: Mean, standard deviation and mean of positive pixels were significantly lower in sections expressing VEGF. For example at SSF 6 mm, median (inter-quartile range) of mean, standard deviation and mean of positive pixels in those with VEGF expression were 150.1 (134.7), 132.4 (49.2) and 184.0 (91.4) vs. 362.5 (150.2), 216.3 (100.1) and 416.6 (80.0) in those without (p = 0.001, p = 0.004 and p = 0.001), respectively. There was a significant association between skewness and MVD (ratio 1.97 (1.15-3.41)) at SSF = 2 mm. CONCLUSIONS: Contrast-enhanced MRI texture analysis features significantly differ according to the presence or absence of histological markers of hypoxia and angiogenesis in CD

Semantic variant primary progressive aphasia: Practical recommendations for treatment from 20 years of behavioural research

People with semantic variant primary progressive aphasia (svPPA) present with a char-acteristic progressive breakdown of semantic knowledge. There are currently no pharmacological interventions to cure or slow svPPA, but promising behavioural approaches are increasingly reported. This article offers an overview of the last two decades of research into interventions to support language in people with svPPA including recommendations for clinical practice and future research based on the best available evidence. We offer a lay summary in English, Spanish and French for education and dissemination purposes. This paper discusses the implications of right-versus left-predominant atrophy in svPPA, which naming therapies offer the best outcomes and how to capitalise on preserved long-term memory systems. Current knowledge regarding the maintenance and generalisation of language therapy gains is described in detail along with the development of compensatory approaches and educational and support group programmes. It is concluded that there is evidence to support an integrative framework of treatment and care as best practice for svPPA. Such an approach should combine rehabilitation interventions addressing the language impairment, compensatory approaches to support activities of daily living and provision of education and support within the context of dementia

Generation of Ultrastable Microwaves via Optical Frequency Division

There has been increased interest in the use and manipulation of optical fields to address challenging problems that have traditionally been approached with microwave electronics. Some examples that benefit from the low transmission loss, agile modulation and large bandwidths accessible with coherent optical systems include signal distribution, arbitrary waveform generation, and novel imaging. We extend these advantages to demonstrate a microwave generator based on a high-Q optical resonator and a frequency comb functioning as an optical-to-microwave divider. This provides a 10 GHz electrical signal with fractional frequency instability <8e-16 at 1 s, a value comparable to that produced by the best microwave oscillators, but without the need for cryogenic temperatures. Such a low-noise source can benefit radar systems, improve the bandwidth and resolution of communications and digital sampling systems, and be valuable for large baseline interferometry, precision spectroscopy and the realization of atomic time

Use of Caval Subtraction 2D Phase-Contrast MR Imaging to Measure Total Liver and Hepatic Arterial Blood Flow: Preclinical Validation and Initial Clinical Translation

Purpose To validate caval subtraction two-dimensional (2D) phase-contrast magnetic resonance (MR) imaging measurements of total liver blood flow (TLBF) and hepatic arterial fraction in an animal model and evaluate consistency and reproducibility in humans. Materials and Methods Approval from the institutional ethical committee for animal care and research ethics was obtained. Fifteen Sprague-Dawley rats underwent 2D phase-contrast MR imaging of the portal vein (PV) and infrahepatic and suprahepatic inferior vena cava (IVC). TLBF and hepatic arterial flow were estimated by subtracting infrahepatic from suprahepatic IVC flow and PV flow from estimated TLBF, respectively. Direct PV transit-time ultrasonography (US) and fluorescent microsphere measurements of hepatic arterial fraction were the standards of reference. Thereafter, consistency of caval subtraction phase-contrast MR imaging-derived TLBF and hepatic arterial flow was assessed in 13 volunteers (mean age, 28.3 years ± 1.4) against directly measured phase-contrast MR imaging PV and proper hepatic arterial inflow; reproducibility was measured after 7 days. Bland-Altman analysis of agreement and coefficient of variation comparisons were undertaken. Results There was good agreement between PV flow measured with phase-contrast MR imaging and that measured with transit-time US (mean difference, -3.5 mL/min/100 g; 95% limits of agreement [LOA], ±61.3 mL/min/100 g). Hepatic arterial fraction obtained with caval subtraction agreed well with those with fluorescent microspheres (mean difference, 4.2%; 95% LOA, ±20.5%). Good consistency was demonstrated between TLBF in humans measured with caval subtraction and direct inflow phase-contrast MR imaging (mean difference, -1.3 mL/min/100 g; 95% LOA, ±23.1 mL/min/100 g). TLBF reproducibility at 7 days was similar between the two methods (95% LOA, ±31.6 mL/min/100 g vs ±29.6 mL/min/100 g). Conclusion Caval subtraction phase-contrast MR imaging is a simple and clinically viable method for measuring TLBF and hepatic arterial flow. Online supplemental material is available for this article